BACE-1 inhibitors part 3: Identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells

被引：44

作者：

Beswick, Paul ^{[1
]}

Charrier, Nicolas ^{[1
]}

Clarke, Brian ^{[1
]}

Demont, Emmanuel ^{[1
]}

Dingwall, Colin ^{[1
]}

Dunsdon, Rachel ^{[1
]}

Faller, Andrew ^{[1
]}

Gleave, Robert ^{[1
]}

Hawkins, Julie ^{[1
]}

Hussain, Ishrut ^{[1
]}

Johnson, Christopher N. ^{[1
]}

MacPherson, David ^{[1
]}

Maile, Graham ^{[1
]}

Matico, Rosalie ^{[1
]}

Milner, Peter ^{[1
]}

Mosley, Julie ^{[1
]}

Naylor, Alan ^{[1
]}

O'Brien, Alistair ^{[1
]}

Redshaw, Sally ^{[1
]}

Riddell, David ^{[1
]}

Rowland, Paul ^{[1
]}

Skidmore, John ^{[1
]}

Soleil, Virginie ^{[1
]}

Smith, Kathrine J. ^{[1
]}

Stanway, Steven ^{[1
]}

Stemp, Geoffrey ^{[1
]}

Stuart, Alistair ^{[1
]}

Sweitzer, Sharon ^{[1
]}

Theobald, Pam ^{[1
]}

Vesey, David ^{[1
]}

Walter, Daryl S. ^{[1
]}

Ward, John ^{[1
]}

Wayne, Gareth ^{[1
]}

机构：

[1] GloxoSmithKlin R&D, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CA19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 03期

关键词：

Alzheimer; BACE-1; aspartic protease; hydroxy ethylamine;

D O I：

10.1016/j.bmcl.2007.12.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1022 / 1026

页数：5

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